2-cyclopentyl-6-hydroxybenzo[d]isothiazol-3(2H)-one | 1135317-57-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻唑类
• 英文名称: 2-cyclopentyl-6-hydroxybenzo[d]isothiazol-3(2H)-one
• 英文别名: 2-cyclopentyl-6-hydroxy-1,2-benzothiazol-3-one
• CAS: 1135317-57-5
• 化学式: C₁₂H₁₃NO₂S
• 分子量: 235.307
• InChiKey: RZEPNZGXSMEBKA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  16
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  65.8
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-cyclopentyl-6-hydroxybenzo[d]isothiazol-3(2H)-one 在 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 作用下， 以 乙二醇二甲醚 、 乙腈 为溶剂， 反应 13.0h， 生成 3-[3-[(2-Cyclopentyl-3-oxo-1,2-benzothiazol-6-yl)oxymethyl]phenyl]-5-nitrobenzoic acid
  参考文献：
  名称：

  Orally Active Metabotropic Glutamate Subtype 2 Receptor Positive Allosteric Modulators: Structure–Activity Relationships and Assessment in a Rat Model of Nicotine Dependence

  摘要：

  Compounds that modulate metabotropic glutamate subtype 2 (mGlu(2)) receptors have the potential to treat several disorders of the central nervous system (CNS) including drug dependence. Herein we describe the synthesis and structure-activity relationship (SAR) studies around a series of mGlu(2) receptor positive allosteric modulators (PAMs). The effects of N-substitution (R-1) and substitutions on the aryl ring (R-2) were identified as key areas for SAR exploration (Figure 3). Investigation of the effects of varying substituents in both the isoindolinone (2) and benzisothiazolone (3) series led to compounds with improved in vitro potency and/or efficacy. In addition, several analogues exhibited promising pharmacokinetic (PK) properties. Furthermore, compound 2 was shown to dose-dependently decrease nicotine self-administration in rats following oral administration. Our data, showing for the first time efficacy of an mGlu(2) receptor PAM in this in vivo model, suggest potential utility for the treatment of nicotine dependence in humans.

  DOI：

  10.1021/jm3005306
• 作为产物：
  描述：

  4-甲氧基硫代水杨酸甲酯 在 三甲基铝 、 三溴化硼 、 三氟乙酸 、 [双(三氟乙酰氧基)碘]苯 作用下， 以 二氯甲烷 、 甲苯 、 苯 为溶剂， 反应 14.0h， 生成 2-cyclopentyl-6-hydroxybenzo[d]isothiazol-3(2H)-one
  参考文献：
  名称：

  Design and Synthesis of an Orally Active Metabotropic Glutamate Receptor Subtype-2 (mGluR2) Positive Allosteric Modulator (PAM) That Decreases Cocaine Self-Administration in Rats

  摘要：

  The modification of 3'((2-cyclopentyl-6,7-dimethyl-1-oxo-2,3-dihydro-1 H-inden-5-yloxy)methyl)biphenyl 4-carboxylic acid (BINA, 1) by incorporating heteroatoms into the structure and replacing the cyclopentyl moiety led to the development of new mGluR2 positive allosteric modulators (PAMs) with optimized potency and superior druglike properties These analogues are more potent than 1 in vitro and are highly selective for mGluR2 vs other mGluR subtypes They have significantly improved pharmacokinetic (PK) properties, with excellent oral bioavailability and brain penetration The benzisothiazol-3-one derivative 14 decreased cocaine self-administration in rats, providing proof-of-concept for the use of mGluR2 PAMs for the treatment of cocaine dependence

  DOI：

  10.1021/jm1012165

文献信息

• POSITIVE ALLOSTERIC MODULATORS OF GROUP II MGLURS
  申请人：Cosford Nicholas D. P.

  公开号：US20120071503A1

  公开（公告）日：2012-03-22

  The disclosure provides compounds and compositions, and methods of using these compounds and compositions, as positive allosteric modulators of the metabotropic glutamate subtype 2 (mGlu2) receptor, and for treating CNS disorders associated with the mGlu2 receptor including schizophrenia, anxiety, addiction, e.g. cocaine addiction, nicotine addiction, and the like.

  本公开提供化合物和组合物，以及使用这些化合物和组合物的方法，作为代谢型谷氨酸亚型2（mGlu2）受体的正向变构调节剂，并用于治疗与mGlu2受体相关的中枢神经系统疾病，包括精神分裂症、焦虑症、成瘾等，例如可卡因成瘾、尼古丁成瘾等。
• Positive allosteric modulators of group II mGluRs
  申请人：Cosford Nicholas D. P.

  公开号：US08748632B2

  公开（公告）日：2014-06-10

  The disclosure provides compounds and compositions, and methods of using these compounds and compositions, as positive allosteric modulators of the metabotropic glutamate subtype 2 (mGlu2) receptor, and for treating CNS disorders associated with the mGlu2 receptor including schizophrenia, anxiety, addiction, e.g. cocaine addiction, nicotine addiction, and the like.

  该披露提供了化合物和组合物，以及使用这些化合物和组合物的方法，作为代谢型谷氨酸亚型2（mGlu2）受体的正向变构调节剂，并用于治疗与mGlu2受体相关的中枢神经系统疾病，包括精神分裂症、焦虑、成瘾，例如可卡因成瘾、尼古丁成瘾等。
• US8748632B2
  申请人：——

  公开号：US8748632B2

  公开（公告）日：2014-06-10
• [EN] POSITIVE ALLOSTERIC MODULATORS OF GROUP II MGLURS<br/>[FR] MODULATEURS ALLOSTÉRIQUES POSITIFS DE MGLURS DE TYPE 2
  申请人：SANFORD BURNHAM MED RES INST

  公开号：WO2011116356A2

  公开（公告）日：2011-09-22

  The disclosure provides compounds and compositions, and methods of using these compounds and compositions, as positive ailosteric modulators of the melabotropic glutamatc subtype 2 (mGlu2) receptor, and for treating CNS disorders associated with the mGlu2 receptor including schizophrenia, anxiety, addiction, e.g. cocaine addiction, nicotine addiction, and the like.